Association Between Comorbidity Burden and Outcomes of Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: Insights from the CABANA Trial

Background and Aims Multimorbidity frequently coexists with atrial fibrillation (AF) and complicates treatment decisions. While current guidelines offer selective recommendations for catheter ablation in this group, evidence remains limited. This study aimed to evaluate whether comorbidity burden modifies the effectiveness of catheter ablation versus antiarrhythmic drug therapy. Methods In this post hoc analysis of the CABANA trial, patients were stratified by overall comorbidity burden using a data-driven threshold based on the distribution of 15 prespecified conditions. The primary outcome was a composite of all-cause mortality, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes included cardiovascular hospitalisation, and a composite of all-cause mortality or cardiovascular hospitalisation. Additional outcomes included AF recurrence and AF-related quality of life in a subcohort. Results Of 2,204 patients, 736 had high comorbidity burden (≥4 conditions, based on a data-driven threshold; median age 68.0 [IQR: 63.0–73.0], 67.1% male) and 1,468 had low burden (median age 67.0 [IQR: 61.0–71.0], 60.7% male). Over a median follow-up of 3.9 years (IQR: 2.4–5.1), for the primary outcome, the adjusted hazard ratio for catheter ablation versus drug therapy was 0.62 (95% CI: 0.42–0.93) in patients with high comorbidity burden and 1.16 (95% CI: 0.76–1.77) in those with low burden (interaction P value = 0.038). Secondary outcomes also tended to favour ablation in the high comorbidity burden group. Moreover, catheter ablation significantly reduced AF recurrence, with relative risk reductions of 49% and 40% in the low and high burden groups, respectively. Furthermore, catheter ablation improved AF-related quality of life in both comorbidity groups, with more sustained and pronounced benefits over time in patients with high comorbidity burden. Conclusions Catheter ablation was associated with more favorable clinical outcomes in AF patients with high comorbidity burden, which support broader consideration of ablation in this population, though prospective trials are needed to confirm and guide clinical decision-making in personalised rhythm management.